Orthotopic transplantation of syngeneic murine colon adenocarcinoma cells into the submucosa of the cecum results in a primary tumor that metastasizes both to the mesenteric lymph node and to the liver. In contrast, subcutaneous transplantation of syngeneic murine colon adenocarcinoma cells does not result in metastasis to any secondary organ. Thus, orthotopic transplantation provides a model that simulates the natural history of human colon cancer. The objective of this proposal is to characterize the immunobiology of an orthotopically transplanted murine colonic tumor and compare and contrast it to a subcutaneous transplant of the same cell line. Specific antitumor immunity of the local, regional, and systemic nodes will be evaluated by a micro-leukocyte adherence inhibition (LAI) assay. Furthermore, the potential role of serum blocking factors and suppressor cells in preventing the immune system from functioning as a focus of host resistance, and thus resulting in continued growth and metastases of the primary tumor, will also be evaluated. This project will provide information on the nature of the local, regional, and systemic antitumor response, factors that sequester that response, and its relationship to primary tumor growth and hepatic metastases.